Cefixime is a semi synthetic cephalosporin antibiotic for oral administration. It was first disclosed in U.S. Pat. No. 4,409,214 by Fujisawa Corporation, Japan.
It has a bactericidal action and the mechanism of action is based on inhibition of bacterial cell wall synthesis.
It is indicated for the treatment of infections caused by various gram—positive and gram—negative organisms chiefly uncomplicated urinary tract infections caused by E. coli and P. mirabilis, otitis media caused by H. influenza, M. catarrhalis and S. pyogenes, acute bronchitis and exacerbations of chronic bronchitis caused by S. pneumonia and H. influenza. It is also indicated for uncomplicated gonorrhea caused by N. gonorrhea. It is one of the most prescribed drugs for pediatric use.
Cefixime as a drug is poorly soluble in water. From the point of view of bioavailability, the preferred form of administration of sparingly soluble medicaments such as beta lactam antibiotics is often an aqueous suspension. Cefixime, given orally, is about 40%-50% absorbed whether administered with or without food.
Children 12 years of age or younger receive, e.g., about 8 mg of Cefixime/kg of body weight each day. The recommended dose can be administered alternatively all at once or divided into 2 single doses (e.g., about 4 mg of Cefixime/kg of body weight in the morning and evening). An increase in the daily dose to 2.×6 mg of Cefixime/kg of body weight is possible depending on the severity and the location of the infection. Adults and children above 12 years of age may receive 400 mg of Cefixime each day. The recommended daily dose may be administered alternatively all at once or divided into 2 single doses (in the morning and evening). The dose should be reduced for patients with distinctly impaired renal function.
Solid dosage forms such as tablets and capsules have certain disadvantages since they have to disintegrate in the gastrointestinal tract and then the medicament has to dissolve before it can be absorbed, thus leading to slower absorption as compared to that of the suspension dosage form and also the absorption is less than the suspension dosage form leading to bioequivalence issues. Also, certain patient populations such as pediatrics and geriatrics have difficulty in swallowing tablets and capsules, and there is a practical limit to the size, and therefore the dose, that can be swallowed.
The oral suspension dosage forms have certain advantages over the above mentioned dosage forms especially in population segments such as pediatrics and geriatrics who have problems in swallowing the solid dosage forms. Further The oral suspension dosage form produces average peak concentrations approximately 25%-50% higher than the conventional tablets. The area under the time versus concentration curve is greater by approximately 10%-25% with the oral suspension than with the conventional tablet after doses of 100 to 400 mg, when tested in normal adult volunteers.
U.S. Pat. No. 4,079,138 by American Home Products Corporation describe a permanent suspension with a non-aqueous basis as vehicle for active substances, which are sensitive to hydrolysis.
U.S. Pat. No. 5,776,926 by Merck discloses Cefixime compositions in the form of non-aqueous suspensions.
Cefixime is currently available in a number of different formulations in various strengths for adult and pediatric patients, for example as tablets comprising 200 mg and 400 mg Cefixime and as oral suspension comprising 100 mg/5 ml Cefixime.
In some patient population the compliance for the currently available oral suspension is low due to requirement of dosing greater than 100 mg in certain disease conditions. Lack of availability of a oral suspension dosage form comprising greater than 100 mg/5 ml cefixime leads to low compliance rates. This is due to multiple dosing required leading to low compliance rates (e.g.; spillage).
There is a need to develop a higher strength oral suspension in unit dose for improving the patient compliance and for reducing the frequency of dosing.